The work proposed in this application is designed to increase our basic and clinical knowledge of reproductive processes in the male with particular relevance to contraception. The focus of our work is on the biochemical, hormonal and genetic control of mammalian spermatogenesis, including applied studies in normal men, with the goal of developing new, clinically approved contraceptives for men throughout the world. We have four research projects: 1) Novel ALDH1a2 Inhibitors for Male Contraception (Dr. J. Amory, P.I.); 2) Retinaldehyde Dehydrogenases as Male Contraceptive Targets (Dr. M. Griswold, P.I.); 3) Spermatogonial Stem Cell Self-Renewal and Differentiation (Dr. R. Braun, P.I.); and 4) Effects of Male Hormonal Contraceptives on Risk Factors for Cardiovascular Disease (Dr. S. Page, P.I.). We also propose an Administration Core Unit, which includes a Program for Fellows and New Investigators. Our proposal incorporates the talents of outstanding investigators of varied backgrounds and professional training into an interactive research program in reproductive biology. We have structured this Center to meld superb science with the practical goal of applying new basic knowledge as quickly as possible to studies in human beings. We hope that, in this way, our work will address critical needs of society.